Interaction between TNFone and tetrapyrroles may account for their anti-genotoxic effects — a novel mechanism for DNA-protection

Autor(en)

Christine Mölzer, Hedwig Huber, Andrea Steyrer, Gesa Viktoria Ziesel, Marlies Wallner, Iryna Goncharova, Sergey Orlov, Marie Urbanová, Charles E. Ahlfors, Libor Vítek, Andrew Cameron Bulmer, Karl-Heinz Wagner

Abstrakt

Bilirubin, the principal and biologically most relevant bile pigment was, until recently, considered a waste product of haem catabolism. However, current data suggest that bile pigments possess biological potential, related to their antioxidant and anti-mutagenic effects. In this context, it is now assumed that bile pigments and their derivatives exert these effects via multiple mechanisms, including discrete anti-oxidative and physico-chemical interactive effects. The major scientific focus so far has concentrated on the compounds' antioxidant action, and mechanistic investigations of possible mutagen-tetrapyrrole interaction are lacking. Therefore we tested structurally related bile pigments/derivatives (bilirubin/-ditaurate/-dimethyl ester, biliverdin/-dimethyl ester, urobilin, stercobilin and protoporphyrin) for anti-genotoxicity in the Salmonella reverse mutation assay (strains TA98, TA102), together with the synthetic mutagen 2,4,7-trinitro-9H-fluoren-9-one (TNFone). To explore possible structural interactions, molecular systems of chlorin e6 porphyrin/bilirubin/biliverdin with TNFone were assayed using circular dichroism. These data consistently revealed, at suprastoichiometric concentrations, that tetrapyrroles interact with TNFone. Addition of TNFone to chlorin e6 porphyrin, bilirubin-albumin and biliverdin-albumin led to a marked change in pigment spectra, providing evidence for tight tetrapyrrole-mutagen interaction. This conclusion was also supported by substantial, TNFone-induced decrease of bilirubin oxidation in the bilirubin-albumin system. This outcome was reflected in a bacterial model, in which most tetrapyrroles and especially protoporphyrin, significantly attenuated TNFone-induced mutagenesis. These data indicate that aromatic, tetrapyrrolic molecules interact with TNFone, providing a novel mechanism to suggest the anti-mutagenic effects of bile pigments in vivo are related to their physico-chemical interaction with genotoxins.

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

University of Chemistry and Technology, Prague, Stanford University, Charles University Prague, Griffith University

Journal

Journal of Porphyrins and Phthalocyanines

Band

Seiten

1-10

Anzahl der Seiten

ISSN

1088-4246

DOI

https://doi.org/10.1142/S1088424613500995

Publikationsdatum

12-2013

Peer-reviewed

ÖFOS 2012

303009 Ernährungswissenschaften

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/interaction-between-tnfone-and-tetrapyrroles-may-account-for-their-antigenotoxic-effects--a-novel-mechanism-for-dnaprotection(a1b2b609-fbbf-4932-b34b-d29a5ec7ebad).html